Synthesis of Novel Bis(thiazolylchromen-2-one) Derivatives Linked to Alkyl Spacer via Phenoxy Group

Article abstract of DOI:10.1002/jhet.3296

A novel series of bis(thiazolylchromen-2-one) derivatives 8 were prepared in good yields by the reaction of the appropriate bis(α-bromoketones) 7 with 2-(1-(2-oxo-2H-chromen-3-yl)ethylidene) hydrazinecarbothioamide (6) in refluxing EtOH in the presence of

Full text of DOI:10.1002/jhet.3296

Month 2018
Synthesis of Novel Bis(thiazolylchromen-2-one) Derivatives Linked to
Alkyl Spacer via Phenoxy Group
Mohamed Hosny, Mostafa E. Salem, Ahmed F. Darweesh, and Ahmed H. M. Elwahy*
Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt
*
E-mail: aelwahy@hotmail.com
Received April 4, 2018
DOI 10.1002/jhet.3296
Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com).
A novel series of bis(thiazolylchromen-2-one) derivatives 8 were prepared in good yields by the reaction
of
the
appropriate
bis(α-bromoketones)
7
with
2-(1-(2-oxo-2H-chromen-3-yl)ethylidene)
hydrazinecarbothioamide (6) in refluxing EtOH in the presence of few drops of TEA. Some other isomeric
derivatives of bis(thiazolylchromen-2-one) 11 and 13 were also successfully obtained by the reaction of
bromoacetylcoumarin 9 with the corresponding bis(ethan-1-yl-1-ylidene))bis(hydrazinecarbothioamides)
1
0 and 12. The structures of the new compounds were established based on elemental analyses as well as
spectral data.
J. Heterocyclic Chem., 00, 00 (2018).
INTRODUCTION
In addition, among libraries of derivatized heterocycles,
the most active library compounds were reported to have
Thiazole derivatives were reported to exhibit a wide
variety of biological activities, such as anti-HIV, anti-
inflammatory, antimicrobial, antihypertensive, antifungal,
anticonvulsant, antiviral, anticancer, antimalarial, and
anti-hypolipidemic activities [1–10].
a bis-heterocyclic [29–32]. Molecular hybridization
concept in drug design and development has been recently
established. This concept based on the combination of
two pharmacophores into a single molecular skeleton
aiming at producing a new hybrid compound with dual
modes of action and reduced undesired side effects [33–35].
Motivated by these findings and in conjunction with our
ongoing research work on bis-heterocycles [36–42], we
report herein on the synthesis of novel bis
The usefulness of many thiazole derivatives as
medicines are well established (Fig. 1) [11–15].
Moreover,
coumarins
also
exhibit
various
pharmacological properties such as antifungal, antioxidant,
anticoagulant, antiviral, antiproliferative, antialzheimer,
anticancer, and anti-HIV [16–20]. Coumarin derivatives
were reported to have a wide range of biological activity,
such as anti-inflammatory [21], anticancer [22,23], anti-
coagulant, anti-oxidant, anti-HIV and anti-bacterial [24]. In
addition to the therapeutic activities of coumarin
derivatives, their less damage to normal cells were also
reported [25]. Furthermore, bis-heterocyclic compounds
exhibit various biological activities, including antibacterial,
fungicidal, tuberculostatic, antiamoebic, anthelmintic, and
plant growth regulative properties [26–29].
(thiazolylchromen-2-one)
derivatives
of
expected
biological application based on the presence of two
pharmacophores with dual mode of action.
RESULTS AND DISCUSSION
We are engaged in a project aiming at the synthesis of
hybrid compounds in which two pharmacophoric
moieties are combining in one molecule to produce new
substances with improved affinity and efficacy compared
with the parent drugs.
©
2018 Wiley Periodicals, Inc.

M. Hosny, M. E. Salem, A. F. Darweesh, and A. H. M. Elwahy
Vol 000
Figure 1. Some drugs incorporating thiazole ring.
In this respect, we recently reported the synthesis of bis
pyrazolylthiazoles) 1 by the reaction of the appropriate bis
hydrazinecarbothioamide) with the corresponding
bromoacetylpyrazole in refluxing ethanol in the presence
of few drops of TEA (Fig. 2) [37].
In an attempt to improve the biological properties of
these compounds, we study here the modification of the
structure of 1 by replacement of the pyrazole rings with
coumarin units. We aimed also at making a change in the
molecular skeleton by separation between the two
heterocyclic units. We believe that such modification
should be a well-established approach for designing more
potent drugs with significant increase in activity.
The novel bis(thiazole-4,2-diyl))bis(hydrazin-2-yl-1-
ylidene))bis(ethan-1-yl-1-ylidene))-bis(2H-chromen-2-
ones) 8 in which (ethylidenehydrazinyl) is located
between two thiazole and coumarin rings were prepared
as outlined in Scheme 1. Thus, the reaction of
bis(α-bromoketones) 7a–c with 2-(1-(2-oxo-2H-
chromen-3-yl)ethylidene) hydrazinecarbothioamide (6)
in refluxing EtOH in the presence of few drops of TEA
afforded the corresponding 8a–c in 60–65% yields
(Scheme 1). Compound 7 was obtained by the reaction
of 3 with N-bromosuccinimide (NBS) in the presence of
p-toluenesulfonic acid (p-TsOH). Compound 6 was
obtained by the reaction of 3-acetylcoumarin (2) with
thiosemicarbazide (5) in refluxing EtOH containing few
drops of AcOH.
(
(
For this purpose, the starting building units, 3-
acetylcoumarin (2) [43,44], bis(acetylphenoxy) alkane 3
[45,46], and bis-aldehyde 4 [47,48], were chosen as
Our study was extended to include the synthesis of the
starting materials and were prepared in good yields as
previously reported (Fig. 3).
new
ylidene))bis(thiazole-4,2-diyl))bis(2H-chromen-2-ones)
1a–c, which are isomeric of 8 as outlined in Scheme 2.
Thus, reaction of the bromoacetylcoumarin 9 with the
corresponding bis(ethan-1-yl-1-ylidene))bis(hydrazine
bis(ethan-1-yl-1
ylidene))bis(hydrazin-1-yl-2-
1
carbothioamide) derivatives 10a–c in refluxing EtOH in
the presence of few drops of TEA afforded 11a–c in 70–
7
8% yields.
Compound 10 was obtained upon treatment of 3 with
thiosemicarabazide 5 in refluxing ethanol containing few
drops of acetic acid (Scheme 2). Compound 9 was
Figure 2. Recently synthesized bis(pyrazolylthiazoles) 1.
obtained by bromination of 2 with Br in AcOH.
2
It is noteworthy to mention that attempts to synthesize
each
of
bis(ethan-1-yl-1-ylidene))bis
(hydrazine
carbothioamide) 10d–f and bis(ethan-1-yl-1 ylidene))
bis(hydrazin-1-yl-2-ylidene))bis(thiazole-4,2-diyl))bis(2H-
chromen-2-ones) 11d–f, in which the bis(hydrazine
Figure 3. Starting building units, 3-acetylcoumarin (2), bis-
(acetylphenoxy) alkane 3, and bis-aldehyde 4.
carbothioamide)
and
bis(thiazole-4,2-diyl))bis(2H-
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Synthesis of Novel Bis(thiazolylchromen-2-one) Derivatives Linked to Alkyl
Spacer via Phenoxy Group
Scheme 1. Synthesis of bis(2H-chromen-2-ones) 8.
p
Scheme 2. Synthesis of bis(2H-chromen-2-ones) 11a-c.
chromen-2-ones) are located at the ortho position with
respect to the ether linkage, using a similar approach were
unsuccessful (Fig. 4). This may be explained in terms of
steric hindrance.
bis(thiazole-4,2-diyl))bis(2H-chromen-2-ones) 13 were
obtained in good yields via initial formation of the
corresponding
(Scheme 3).
bis(hydrazinecarbothioamides)
12a–f
When the same methodology was applied utilizing the
bis aldehydes 4a–c or 4d–f as intermediates, the
All of the isolated compounds were characterized by
elemental analyses, as well as their spectral data, which
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. Hosny, M. E. Salem, A. F. Darweesh, and A. H. M. Elwahy
Vol 000
Figure 4. Bis(2H-chromen-2-ones) 11d–f.
Scheme 3. Synthesis of bis(2H-chromen-2-ones) 13.
p
o
agree with the proposed structures. Thus, the IR spectrum
to alkyl spacer via phenoxymethyl group. The new
synthesized compounds are expected to have different
biological functions and dual activity for being as hybrid
molecules with two distinct pharmacophores. The
straightforward synthesis of these compounds in good
yields under mild reaction condition from accessible
starting material should open a new access for novel bis
(functionalized) heterocycles of expected biological and
pharmaceutical activities.
of 13b, as a representative example, showed absorption
ꢀ
1
ꢀ1
bands at 3448 cm due to (NH) and at 1709 cm due
1
to carbonyl stretching frequency. The H NMR spectra of
compound 13b showed a D O-exchangeable signal at δ
2
12.01 due to NH protons, a characteristic singlet signal at
δ 8.01 due to one methine proton (–N=CH–), a sharp
singlet at δ 8.52 attributed to C-5 proton of the thiazole
ring and at δ 7.74 attributed to the C-4 proton of the
chromen ring. Moreover, they also featured the
methylene ether linkage OCH as a singlet signal at δ
2
4.18 ppm. All other protons were seen at the expected
EXPERIMENTAL
chemical shifts and integral values. Mass spectrum of
compound 13b showed a weak molecular ion peak at m/z
General.
Melting points were determined in open
7
66, in agreement with its respective molecular formula.
glass capillaries with a Gallenkamp apparatus and were
not corrected. Infrared spectra were recorded in
potassium bromide disks on a PyeUnicam SP3–300 and
CONCLUSIONS
1
Shimadzu FTIR 8101 PC infrared spectrophotometer. H
13
We have developed an efficient synthesis of a novel
and C NMR spectra were determined on a Varian
Mercury VX 300NMR spectrometer using TMS as an
series of bis (thiazolylchromen-2-ones), which are linked
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Synthesis of Novel Bis(thiazolylchromen-2-one) Derivatives Linked to Alkyl
Spacer via Phenoxy Group
internal standard and DMSO-d6 as a solvent. Mass spectra
were measured on a GC MS-QP1000 EX spectrometer at
heated at reflux for 2–3 h. The solvent was evaporated in
vacuo, and the solid residue was collected by filtration
and recrystallized from ethanol/DMF to give 10a–c.
(2,2 )-2,2 -(((Ethane-1,2-diylbis(oxy))bis(4,1-phenylene))
bis(ethan-1-yl-1-ylidene))bis(hydrazinecarbothioamide)
70 eV. Elemental analyses were carried out at the
0
0
Microanalytical Center of Cairo University, Giza, Egypt.
The starting 6 [49], 7a-c [50], 9 [51], and 12a–f [37] were
prepared following literature procedures.
General procedure for the synthesis of alkane-diylbis(oxy))
bis(phenylene))bis-(thiazole-4,2-diyl))bis(hydrazin-2-yl-1-
ylidene))bis(ethan-1-yl-1-ylidene))bis(2H-chromen-2-one)
(
10a).
This compound was obtained as white crystal,
(81% yield), mp 280–282°C; ir (potassium bromide): NH
ꢀ
1 1
3406, NH 3235, 3145, CS 1664, C=N 1593 cm ; H
2
nmr: δ 2.26 (s, 6H, CH ), 4.36 (s, 4H, CH O), 6.97 (d,
3
2
8
a–c.
To a solution of 2-(1-(2-oxo-2H-chromen-3-yl)
4
H, J = 8.7 Hz), 7.89 (d, 4H, J = 9.0 Hz), 8.18 (br. s,
ethylidene) hydrazinecarbothioamide (6) (2 mmol) and
bis(2-bromoethanone) derivatives 7a–c (1 mmol) in
ethanol (25 mL), few drops of TEA were added. The
reaction mixture was heated at reflux for 4 h. The solvent
was evaporated in vacuo, and the solid residue was
collected by filtration and recrystallized from
ethanol/DMF to give 8a–c.
4
H, NH ), 10.06 ppm (br. s, 2H, NH); ms: m/z (%) 444
2
+
(0.11, M ). Anal. Calcd for C H N O S : C, 54.03; H,
20 24 6 2 2
5
.44; N, 18.90; S, 14.43. Found: C, 54.10; H, 5.33; N,
1
8.81; S, 14.38.
0
0
(
2,2 )-2,2 -(((Propane-1,3-diylbis(oxy))bis(4,1-phenylene))
bis(ethan-1-yl-1-ylidene))bis(hydrazinecarbothioamide)
(10b).
This compound was obtained as white crystal,
83% yield), mp 225–227°C; ir (potassium bromide): NH
0
0
0
0
3
,3 -((1,1 )-(2,2 -(4,4 -((Ethane-1,2-diylbis(oxy))bis(4,1-
(
phenylene))bis(thiazole-4,2-diyl))bis(hydrazin-2-yl-1-ylidene))
ꢀ1
1
3
393, NH 3199, 3136, CS 1672, C=N 1591 cm ; H
2
bis(ethan-1-yl-1-ylidene))bis(2H-chromen-2-one) (8a).
This
nmr: δ 2.18 (m, 2H, CH ), 2.25 (s, 6H, CH ), 4.17 (t,
2
3
compound was obtained as creamy powder, (73% yield),
mp >300°C; ir (potassium bromide): NH 3430, CO
4
H, J = 6.3 Hz, CH O), 6.94 (d, 4H, J = 8.7 Hz), 7.86
2
ꢀ
1
1
(d, 4H, J = 9.0 Hz), 8.17 (br. s, 4H, NH
2
), 10.08 ppm
br. s, 2H, NH); C nmr: δ 13.73, 28.53, 64.32, 114.11,
28.05, 130.12, 147.80, 159.43, 178.71; ms: m/z (%) 458
1
4
2
721, C=N 1603 cm ; H nmr: δ 2.21 (s, 6H, CH ),
3
13
(
1
.61 (s, 4H, CH O), 7.02–7.75 (m, 16H, ArH), 7.95 (s,
H, thiazole-5-H), 8.03 (s, 2H, chromen-4-H), 11.23 ppm
s, 2H, NH); ms: m/z (%) 780 (0.21, M ). Anal. Calcd for
2
+
+
(0.36, M ). Anal. Calcd for C21
H
N
26
O
6
2
S
2
: C, 55.00; H,
.71; N, 18.33; S, 13.98. Found: C, 54.96; H, 5.63; N,
8.25; S, 13.89.
(
5
1
C H N O S : C, 64.60; H, 4.13; N, 10.76; S, 8.21.
4
2 32 6 6 2
Found: C, 64.49; H, 4.05; N, 10.66; S, 8.17.
0
0
0
0
0
0
(2,2 )-2,2 -(((Butane-1,4-diylbis(oxy))bis(4,1-phenylene))
bis(ethan-1-yl-1-ylidene))bis(hydrazinecarbothioamide)
10c).
3
,3 -((1,1 )-(2,2 -(4,4 -((Propane-1,3-diylbis(oxy))bis(4,1-
phenylene))bis(thiazole-4,2-diyl))bis(hydrazin-2-yl-1-ylidene))
(
(
This compound was obtained as white crystal,
82% yield), mp 250–252°C; ir (potassium bromide): NH
bis(ethan-1-yl-1-ylidene))bis(2H-chromen-2-one) (8b).
This
compound was obtained as creamy powder, (78% yield),
mp >300°C; ir (potassium bromide): NH 3429, CO
ꢀ
1 1
3
392, NH 3208, 3140, CS 1673, C=N 1592 cm ; H
2
ꢀ
1 1
nmr: δ 1.88 (br. s, 4H, CH ), 2.26 (s, 6H, CH ), 4.07 (br.
s, 4H, CH O), 6.92 (d, 4H, J = 9.0 Hz), 7.86 (d, 4H,
J = 9.0 Hz), 8.17 (br. s, 4H, NH ), 10.08 ppm (br. s, 2H,
NH); ms: m/z (%) 472 (0.25, M ). Anal. Calcd for
C H N O S : C, 55.91; H, 5.97; N, 17.78; S, 13.57.
Found: C, 55.88; H, 5.90; N, 17.83; S, 13.48.
General procedure for the synthesis of bis(ethan-1-yl-1-
ylidene))bis(hydrazin-1-yl-2-ylidene))bis(thiazole-4,2-diyl))
bis(2H-chromen-2-ones) 11a–c. To a solution of bis (ethan-
1
2
1
720, C=N 1603 cm ; H nmr: δ 2.21 (br. s, 2H, CH ),
2
3
2
.27 (s, 6H, CH ), 4.18 (br. s, 4H, CH O), 6.99–7.86 (m,
6H, ArH), 7.94 (s, 2H, thiazole-5-H), 8.14 (s, 2H,
2
3
2
2
+
chromen-4-H), 11.37 ppm (br. s, 2H, NH); ms: m/z (%)
+
7
6
4
94 (0.32, M ). Anal. Calcd for C H N O S : C,
22 28 6 2 2
4
3 34 6 6 2
4.97; H, 4.31; N, 10.57; S, 8.07. Found: C, 64.91; H,
.28; N, 10.51; S, 7.98.
,3 -((1,1 )-(2,2 -(4,4 -((Butane-1,4-diylbis(oxy))bis(4,1-
0
0
0
0
3
phenylene))bis(thiazole-4,2-diyl))bis(hydrazin-2-yl-1-ylidene))
bis(ethan-1-yl-1-ylidene))bis(2H-chromen-2-one) (8c).
This
1-yl-1-ylidene))bis(hydrazinecarbothioamide) derivatives
10a–c (1 mmol) and 3-(2-bromoacetyl)-2H-chromen-2-
one (9) (2 mmol) in ethanol (25 mL), few drops of TEA
were added. The reaction mixture was heated at reflux for
4 h. The solvent was evaporated in vacuo, and the solid
residue was collected by filtration and recrystallized from
ethanol/DMF to give 11a–c.
compound was obtained as creamy powder, (76% yield),
mp 285–287°C; ir (potassium bromide): NH 3434, CO
ꢀ
1 1
1
2
1
1
713, C=N 1603 cm ; H nmr: δ 1.90 (br. s, 4H, CH ),
2
.28 (s, 6H, CH ), 4.06 (br. s, 4H, CH O), 6.96–7.81 (m,
8H, ArH & thiazole-5-H), 8.15 (s, 2H, chromen-4-H),
1.31 ppm (br. s, 2H, NH); ms: m/z (%) 808 (0.38, M ).
3
2
+
0
0
0
0
Anal. Calcd for C H N O S : C, 65.33; H, 4.49; N,
3,3 -(2,2 -((2,2 )-2,2 -(((Ethane-1,2-diylbis(oxy))bis(4,1-phenylene))
bis(ethan-1-yl-1-ylidene))bis(hydrazin-1-yl-2-ylidene))bis(thiazole-4,2-
diyl))bis(2H-chromen-2-one) (11a). This compound was
4
4 36 6 6 2
1
0.39; S, 7.93. Found: C, 65.25; H, 4.40; N, 10.35; S, 7.87.
General procedure for the synthesis of bis(ethan-1-yl-1-
ylidene))bis(hydrazine-carbothioamide) derivatives 10a–c.
To a solution of bis acetyl derivatives 3a–c (1 mmol) and
thiosemicarbazide (5) (2 mmol) in ethanol (25 mL), few
drops of AcOH were added. The reaction mixture was
obtained as orange crystals, (70% yield), mp >300°C; ir
(potassium bromide): NH 3428, CO 1715, C=N
ꢀ
1 1
1569 cm ; H nmr: δ 2.30 (s, 6H, CH
CH O), 7.02–7.10 (m, 6H, ArH), 7.35–7.91 (m, 10H,
), 4.36 (s, 4H,
3
2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. Hosny, M. E. Salem, A. F. Darweesh, and A. H. M. Elwahy
Vol 000
0
0
0
0
ArH), 7.94 (s, 2H, chromen-4-H), 8.56 (s, 2H, thiazole-5-
3,3 -(2,2 -((2,2 )-2,2 -(((Propane-1,3-diylbis(oxy))bis(4,1-
phenylene))bis(methanylylidene))bis(hydrazin-1-yl-2-ylidene))
H), 11.16 ppm (br. s, 2H, NH); ms: m/z (%) 780 (0.11,
+
bis(thiazole-4,2-diyl))bis(2H-chromen-2-one) (13b).
This
M ). Anal. Calcd for C H N O S : C, 64.60; H, 4.13;
4
2 32 6 6 2
compound was obtained as yellow crystals, (77% yield),
N, 10.76; S, 8.21. Found: C, 64.49; H, 4.22; N, 10.71; S,
.16.
mp 272–274°C; ir (potassium bromide): NH 3448, CO
8
ꢀ
1 1
0
0
0
0
3
,3 -(2,2 -((2,2 )-2,2 -(((Propane-1,3-diylbis(oxy))bis(4,1-
1709, C=N 1576 cm ; H nmr: δ 2.20 (br. s, 2H, CH ),
2
phenylene))bis(ethan-1-yl-1-ylidene))bis(hydrazin-1-yl-2-
4.18 (br. s, 4H, CH O), 7.02 (d, 4H, J = 7.8 Hz), 7.35–
2
ylidene))bis(thiazole-4,2-diyl))bis(2H-chromen-2-one) (11b).
This compound was obtained as orange crystals, (78%
7.44 (m, 4H, ArH), 7.59 (d, 4H, J = 8.1 Hz), 7.74 (s, 2H,
chromen-4-H), 7.82–7.84 (m, 4H, ArH), 8.01 (s, 2H,
CH=N), 8.52 (s, 2H, thiazole-5-H), 12.01 ppm (s, 2H,
yield), mp 254–256°C; ir (potassium bromide): NH
ꢀ
1 1
+
3
428, CO 1718, C=N 1562 cm ; H nmr: δ 2.20 (t, 2H,
NH); ms: m/z (%) 766 (0.16, M ). Anal. Calcd for
J = 6.0 Hz, CH ), 2.29 (s, 6H, CH ), 4.18 (t, 4H,
2
3
C H N O S : C, 64.22; H, 3.94; N, 10.96; S, 8.36.
41 30 6 6 2
J = 6.0 Hz, CH O), 7.00 (d, 4H, J = 8.7 Hz), 7.37–7.45
Found: C, 64.26; H, 3.87; N, 10.89; S, 8.29.
2
0
0
0
0
(
m, 4H, ArH), 7.59–7.81 (m, 10H, ArH & chromen-4-
3,3 -(2,2 -((2,2 )-2,2 -(((Butane-1,4-diylbis(oxy))bis(4,1-
H), 8.56 (s, 2H, thiazole-5-H), 11.19 ppm (br. s, 2H,
NH); ms: m/z (%) 794 (0.36, M ). Anal. Calcd for
phenylene))bis(methanylylidene))bis(hydrazin-1-yl-2-ylidene))
+
bis(thiazole-4,2-diyl))bis(2H-chromen-2-one) (13c).
This
compound was obtained as yellow crystals, (75% yield),
C H N O S : C, 64.97; H, 4.31; N, 10.57; S, 8.07.
4
3 34 6 6 2
mp 278–280°C; ir (potassium bromide): NH 3444, CO
Found: C, 64.88; H, 4.24; N, 10.59; S, 8.00.
ꢀ
1 1
0
0
0
0
3
,3 -(2,2 -((2,2 )-2,2 -(((Butane-1,4-diylbis(oxy))bis(4,1-
1707, C=N 1569 cm ; H nmr: δ 1.90 (br. s, 4H, CH ),
2
phenylene))bis(ethan-1-yl-1-ylidene))bis(hydrazin-1-yl-2-
ylidene))bis(thiazole-4,2-diyl))bis(2H-chromen-2-one) (11c).
This compound was obtained as orange crystals, (76%
4.09 (br. s, 4H, CH O), 7.00 (d, 4H, J = 8.7 Hz), 7.36–
2
7.45 (m, 4H, ArH), 7.59 (d, 4H, J = 8.7 Hz), 7.74 (s, 2H,
chromen-4-H), 7.83–7.85 (m, 4H, ArH), 8.01 (s, 2H,
CH=N), 8.53 (s, 2H, thiazole-5-H), 12.01 ppm (s, 2H,
yield), mp 240–242°C; ir (potassium bromide): NH 3395,
ꢀ
1 1
+
CO 1719, C=N 1593 cm ; H nmr: δ 1.87 (br. s, 4H,
CH ), 2.25 (s, 6H, CH ), 4.06 (br. s, 4H, CH O), 6.91 (d,
NH); ms: m/z (%) 780 (0.13, M ). Anal. Calcd for
2
3
2
C H N O S : C, 64.60; H, 4.13; N, 10.76; S, 8.21.
42 32 6 6 2
4
H, J = 8.7 Hz), 6.95–7.91 (m, 8H, ArH), 7.84 (d, 4H,
Found: C, 64.45; H, 4.06; N, 10.66; S, 8.17.
0
0
0
0
J = 8.7 Hz), 8.12 (s, 2H, chromen-4-H), 8.55 (s, 2H,
thiazole-5-H), 10.03 ppm (s, 2H, NH); C nmr: δ 13.73,
2
1
1
3,3 -(2,2 -((2,2 )-2,2 -(((Ethane-1,2-diylbis(oxy))bis(2,1-
1
3
phenylene))bis(methanylylidene))bis(hydrazin-1-yl-2-ylidene))
bis(thiazole-4,2-diyl))bis(2H-chromen-2-one) (13d).
compound was obtained as yellow crystals, (66%
This
5.32, 67.23, 110.75, 114.07, 114.30, 115.79, 119.12,
24.63, 127.07, 128.03, 128.60, 129.97, 130.23, 130.36,
yield), mp 276–278°C; ir (potassium bromide): NH
37.88, 147.85, 159.58, 169.34, 178.71; ms: m/z (%) 808
ꢀ
1
1
+
3414, CO 1695, C=N 1572 cm ; H nmr: δ 4.46 (s,
(0.15, M ). Anal. Calcd for C H N O S : C, 65.33; H,
4
4 36 6 6 2
4
H, CH O), 7.07–7.41 (m, 12H, ArH), 7.59–7.85 (m,
4
1
.49; N, 10.39; S, 7.93. Found: C, 65.42; H, 4.54; N,
0.33; S, 7.81.
General procedure for the synthesis of bis(2H-chromen-2-
2
6
H, ArH & chromen-4-H), 8.43 (br. s, 4H, thiazole-5-
H & CH=N), 12.08 ppm (s, 2H, NH); ms: m/z (%)
+
one)thiazol-2-yl)hydrazono)methyl)phenoxy) alkane 13a–f.
752 (0.13, M ). Anal. Calcd for C H N O S : C,
4
0 28 6 6 2
To
bis(methan-1-yl-1-ylidene))bis (hydrazine-carbothioamide)
2a–f (1 mmol) and 3-(2-bromoacetyl)-2H-chromen-2-one
9) (2 mmol) in ethanol (25 mL), few drops of TEA were
a
solution of alkylenebis(oxy)bis(2,1-phenylene)
63.82; H, 3.75; N, 11.16; S, 8.52. Found: C, 63.70; H,
3.82; N, 11.23; S, 8.43.
0
0
0
0
3
,3 -(2,2 -((2,2 )-2,2 -(((Propane-1,3-diylbis(oxy))bis(2,1-
phenylene))bis(methanylylidene))bis(hydrazin-1-yl-2-ylidene))
bis(thiazole-4,2-diyl))bis(2H-chromen-2-one) (13e).
1
(
This
added. The reaction mixture was heated at reflux for 4 h.
The solvent was evaporated in vacuo, and the solid residue
was collected by filtration and recrystallized from
ethanol/DMF to give 13a–f.
compound was obtained as orange crystals, (72% yield),
mp 216–218°C; ir (potassium bromide): NH 3429, CO
ꢀ
1
1
1716, C=N 1567 cm
;
H nmr: δ 2.30 (t, 2H,
0
0
0
0
J = 6.0 Hz, CH ), 4.31 (t, 4H, J = 6.0 Hz, CH O),
3
,3 -(2,2 -((2,2 )-2,2 -(((Ethane-1,2-diylbis(oxy))bis(4,1-
phenylene))bis (methanylylidene))bis(hydrazin-1-yl-2-ylidene))
bis(thiazole-4,2-diyl))bis(2H-chromen-2-one) (13a).
2
2
6.99–7.15 (m, 4H, ArH), 7.34–7.61 (m, 8H, ArH), 7.74
This
(s, 2H, chromen-4-H), 7.77–7.83 (m, 4H, ArH), 8.46
compound was obtained as yellow crystals, (72% yield),
(s, 2H, CH=N), 8.51 (s, 2H, thiazole-5-H), 12.13 ppm
13
mp 280–282°C; ir (potassium bromide): NH 3442, CO
(s, 2H, NH); C nmr: δ 28.78, 64.75, 110.44, 112.72,
115.81, 119.12, 120.49, 120.89, 122.55, 124.63, 124.99,
128.74, 130.73, 131.59, 137.48, 138.06, 143.91, 152.24,
ꢀ
1 1
1
7
8
1
709, C=N 1572 cm ; H nmr: δ 4.36 (s, 4H, CH O),
2
.03–7.94 (m, 16H, ArH), 7.73 (s, 2H, chromen-4-H),
.01 (s, 2H, CH=N), 8.51 (s, 2H, thiazole-5-H),
2.01 ppm (s, 2H, NH); ms: m/z (%) 752 (0.27, M ).
+
156.31, 158.68, 167.60; ms: m/z (%) 766 (0.05, M ).
+
Anal. Calcd for C H N O S : C, 64.22; H, 3.94; N,
41 30 6 6 2
Anal. Calcd for C H N O S : C, 63.82; H, 3.75; N,
10.96; S, 8.36. Found: C, 64.14; H, 3.88; N, 10.86; S,
8.30.
4
0 28 6 6 2
11.16; S, 8.52. Found: C, 63.73; H, 3.69; N, 11.11; S, 8.45.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Synthesis of Novel Bis(thiazolylchromen-2-one) Derivatives Linked to Alkyl
Spacer via Phenoxy Group
0
0
0
0
3
,3 -(2,2 -((2,2 )-2,2 -(((Butane-1,4-diylbis(oxy))bis(2,1-
phenylene))bis(methanylylidene))bis(hydrazin-1-yl-2-ylidene))
bis(thiazole-4,2-diyl))bis(2H-chromen-2-one) (13f).
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This
compound was obtained as yellow crystals, (75% yield),
[
mp 222–225°C; ir (potassium bromide): NH 3440, CO
Almeida, L. D.; Luchini, A. C.; Rodrigues-Orsi, P.; Cestari, S. H.; Di
Stasi, L. C. Phytomedicine 2014, 21, 240.
ꢀ
1 1
1
4
7
7
699, C=N 1573 cm ; H nmr: δ 2.02 (br. s, 4H, CH ),
2
[22] Nasr, T.; Bondock, S.; Youns, M. Eur J Med Chem 2014, 76,
.17 (br. s, 4H, CH O), 7.01–7.13 (m, 4H, ArH), 7.33–
2
539.
.61 (m, 8H, ArH), 7.73 (s, 2H, chromen-4-H), 7.78–
.80 (m, 4H, ArH), 8.48 (s, 2H, CH=N), 8.49 (s, 2H,
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[
J
thiazole-5-H), 12.18 ppm (s, 2H, NH); ms: m/z (%) 780
+
(
0.10, M ). Anal. Calcd for C H N O S : C, 64.60; H,
42 32 6 6 2
[25] Murat Bilgin, H.; Atmaca, M.; Deniz Obay, B.; Özekinci, S.;
4
1
.13; N, 10.76; S, 8.21. Found: C, 64.45; H, 4.19; N,
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet